CTNI-48. SURVIVAL, TOXICITY, AND PATIENT REPORTED QOL OUTCOMES FOLLOWING PULSED REDUCED DOSE RATE RE-IRRADIATION WITH CONCURRENT BEVACIZUMAB FOR RECURRENT GRADE 4 GLIOMAS: RESULTS OF A PHASE II STUDY

Abstract

Abstract Grade 4 gliomas are aggressive primary brain tumors with dismal prognosis despite maximal treatment. Recurrent disease is typically found within the prior radiation treatment field, complicating reirradiation. Pulsed reduced dose rate (PRDR) radiation is a treatment technique that reduces effective dose rate and increases treatment time allowing for intrafraction repair. Bevacizumab is a systemic VEGF inhibitor with efficacy in treating gliomas. We conducted a phase 2 prospective trial combining PRDR radiation with biweekly bevacizumab (10 mg/kg) in patients with recurrent grade 4 gliomas. Radiation was delivered with reduced dose rate delivered in 20 cGy pulses every 3 minutes in 2 Gy daily fractions to a total dose of 54 Gy. Kaplan Meier analysis was utilized to calculate progression free survival (PFS) and overall survival (OS). Toxicities were evaluated based on Common Terminology Criteria for Adverse Event v5.0 criteria. Mini Mental Status Examination (MMSE), as well as FACT-Brain, and FACIT-Fatigue patient reported quality of life (QoL) surveys were collected at baseline and follow up visits. Minimal important difference scores were calculated using by ½ standard deviation method. A total of 36 patients were enrolled, with 77% having previously received additional therapy for recurrent disease prior to study enrollment. Median PFS was 4.9 months and median OS was 6.9 months. No grade 4+ toxicity was observed. Two patients had grade 3 treatment related toxicity (seizure and radiation necrosis, both PRDR related). Treatment related grade 2 toxicity was seen in 44% of patients, primarily fatigue (30%). Clinically significant decrease in mean MMSE score, and FACT-BR QoL metrics across all sub-domains were noted in follow up. No clinically significant difference in mean FACIT-Fatigue QoL metric was observed. In this prospective phase 2 trial, PRDR with concurrent bevacizumab resulted in encouraging survival outcomes with acceptable toxicity in patients with recurrent grade 4 gliomas.